NORDIC was created, to provide the organization and operational capability to perform multi-site observational and treatment trials that address the many crucial yet unanswered questions about risks, diagnosis, treatment and other management-aspects of these diseases, which could not be studied without a clinical research organization. The plan is to create between 100 to 200 community and academic clinical trial sites.
NORDIC’s research strategy is to provide strong central coordination to an open research organization of investigators at community and academic sites, in order to conduct multiple trials, employing protocols that can be incorporated into standard clinical practice. NORDIC management is provided by: 1) governing Chair and Executive Committee (EC) members, comprised of recognized leaders in Neuro-Ophthalmic and clinical research; 2) a Study Steering Committee (SSC) recruited for each individual study; 3) a Data Coordination and Biostatistics Center (DCBC), well-versed in managing the data generated through national, multi-site studies; and 4) reading centers appropriate for significant Neuro-Ophthalmic assessments including a Visual Field Reading Center (VFRC) and a Photo Reading Center (PRC). Additional reading centers will be added as needed for each new study. All data will be stored in the secure DCBC servers. The open group construction allows practitioners to achieve certification and participate in specific studies and protocols, as appropriate to their expertise. Together, the able central command combined with an extensive number of investigators allows for the recruitment and study of significant numbers of otherwise-hard-to-find study patients, with a high degree of control over the scientific quality of the research projects.
NORDIC aims to be: 1) efficient in organizing and focusing research efforts by using a common administrative structure with similar research protocols for studies; 2) cost-effective in comparison to doing individual, smaller and less-definitive studies; and 3) flexible in its potential to eventually implement trials of emerging new therapies and diagnostic strategies, for rapid translation from the laboratory to the clinic. 4) provide a structure for new investigator and industry initiated study design and development.
The products of the NORDIC studies will be evidence-based diagnostic and treatment solutions that can be applied to ophthalmologic and neurological practice to enhance the visual health of a significant portion of the population.
NORDIC will conduct:
- Randomized Controlled Clinical Trials to test the efficacy and safety of treatments for specific sets of Neuro-Ophthalmologic disorders.
- Randomized Controlled Clinical Trials utilizing acute optic nerve injury (eg optic neuritis) as a model to test therapies that have the potential to protect the nervous system (neuroprotection).
- Epidemiological studies, pilot studies and other planning activities to develop new research projects on compelling clinical questions in Neuro-Ophthalmology that will benefit from the NORDIC strategy. New clinical research projects are submitted for appropriate peer review.
- Pilot investigations to explore translational research and develop new controlled clinical trials.
- Studies designed to determine vision toxicity of systemic therapies.
Benefits of NORDIC - An Open Investigator Group to Perform Research
- The Research organization will encourage doctors with interest in Neuro-Ophthalmological disorders to participate in prospective clinical research studies. Investigator certification will depend on the interest and expertise, providing the opportunity to individuals in solo and group practices to be Investigators. The latter investigators should provide practical expertise on efficiently diagnosing and managing the disorders to be studied. The consortium approach also provides the ability to incorporate managed care settings as well as traditional private practice and medical center settings into clinical trials; and this need may become more important as changes in health care delivery continue to occur. This should facilitate developing NORDIC procedures that can be generalized, lead to rapid enrollment of subjects in studies, and make it easier to disseminate results and affect clinical practice using evidence based approaches.
- NORDIC can work in conjunction with various NIH agencies, foundations and industry to expand the concept of performing prospective Neuro-Ophthalmology research in an inclusive manner.
- Young investigators will be encouraged to prepare new proposals and perform pilot clinical studies with the knowledge that the NORDIC EC will mentor and assist in refining proposals, securing adequate pilot project subjects, colleague cooperation, and financial support.
- The studies will demonstrate the utility and rationale of treatments for common neurological and systemic disorders that cause visual disability due to visual system or ocular motor dysfunction.
- NORDIC can conduct long-range observational studies that provide scientific basis for diagnostic evaluations and new therapies. This can include longitudinal cohorts of subjects after participation in a NORDIC treatment trial, particularly when the underlying disorders cause progressive long-term healthcare problems. An important example of the benefit of observational study of a uniform cohort of subjects is the Long Term Optic Neuritis Study, which followed the subjects recruited for the ONTT. The commitment of investigators and the coordinating leadership led to an 88% 10 year follow up and yielded considerably more than initially planned. The results identified clinical risk factors of developing MS, the need for MRI assessment, need for complete clinical examination, and features associated with not developing MS.
- Preliminary or pilot studies can be rapidly put in place to test toxicity of new agents (now frequently mandated by the FDA) or the effects of new therapies for neurological disorders using sophisticated measures of vision, pupillary, and ocular motor function to determine the effects of these treatments.
- Clinical trials are run more efficiently due to the following:
- A single DCBC can manage several trials concurrently with more rapid start up by applying standardized evaluations and protocols, manual of procedures, and standard electronic case report forms (eCRFs) for the standardized evaluations in the same Clinical Data Management System (CDMS) with protocol specific eCRFs created as needed.. Every subsequent study will add experience and knowledge of managing issues specific for neurological and systemic disorders that disturb vision and ocular motor function, and subjects with Neuro-Ophthalmological illnesses.
- A common committee structure can provide oversight, including the internal EC and external Data and Safety Monitoring Committee.
- Site visits can be conducted to audit multiple trials simultaneously and if necessary in future trials to concurrently certify staff at the site. This should be efficiently accomplished using NORDIC Regional Project Coordinators (RPC) who will be located at four participating NORDIC sites around the country. These RPCs will maintain contact with study sites, providing continuity, professional update and support to site personnel.
- New protocols can be developed efficiently and the start-up time to implement a new trial from the inception of the concept for the trial to initiation of recruitment can be greatly shortened.
- Central reading centers (e.g., VFRC, PRC) can develop specific standardized methods of performing tests for Neuro-Ophthalmology disorders with standardized eCRFs in the same CDMS so Investigator sites may be certified in procedures that will be applicable to many NORDIC protocols and will thus need to be certified less often.
- NORDIC will include a large number of qualified, skilled, trained and certified Investigators, which will reduce the recruitment period and include doctors not traditionally involved in clinical trials. NORDIC will improve the clinical diagnostic and management skills that can be used in providing medical care.
- This Research organization of both eye care professionals and neurologists will allow flexibility to create studies that includes a wide spectrum of other specialists, from experts in multiple sclerosis to those with expertise in glaucoma for normal tension glaucoma, to rheumatologists for giant cell arteritis, since many disorders are investigated, diagnosed, and co-managed by Neuro-Ophthalmologists.
Organization and Administration of Research Organization:
The Executive Committee is responsible for all operations of NORDIC, appoints and manages the organizational structure, including all of the committees and functions, and facilitates the interactions between these committees, the DCBC, and the Investigators to perform treatment and observational clinical studies. The EC will recruit and select large numbers of clinical Investigators and sites, including doctors in private practice, to participate in NORDIC studies after holding protocol and skill workshops to train, and certify all Investigators. 45 clinical sites have been selected for the IIHTT.
The administrative structure of NORDIC includes three permanent components: Executive Committee (EC), DCBC, and the NEI appointed Data and Safety Monitoring Committee. An SSCs is directing the IIHTT. New Study Planning and Steering Committees, composed of EC members and NORDIC Investigators, will be created for each study anticipated to receive funding. Investigators will be certified for each study. The NORDIC EC selected a VFRC and PRC for the first studies. Sub-committees of the EC include the Health Related Quality of Life, Credentials, and Publication Committees. Functions of the committees as are defined and in place.